Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, China.
College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, China.
Front Endocrinol (Lausanne). 2023 Jan 19;13:1085408. doi: 10.3389/fendo.2022.1085408. eCollection 2022.
Ubiquitin-fold modifier 1 (UFM1) is a ubiquitin-like molecule (UBL) discovered almost two decades ago, but our knowledge about the cellular and molecular mechanisms of this novel protein post-translational modification is still very fragmentary. In this review, we first summarize the core enzymes and factors involved in the UFMylation cascade, which, similar to ubiquitin, is consecutively catalyzed by UFM1-activating enzyme 5 (UBA5), UFM1-conjugating enzyme 1 (UFC1) and UFM1-specific ligase 1 (UFL1). Inspired by the substantial implications of UFM1 machinery in the secretory pathway, we next concentrate on the puzzling role of UFMylation in maintaining ER protein homeostasis, intending to illustrate the underlying mechanisms and future perspectives. At last, given a robust ER network is a hallmark of healthy endocrine secretory cells, we emphasize the function of UFM1 modification in physiology and pathology in the context of endocrine glands pancreas and female ovaries, aiming to provide precise insight into other internal glands of the endocrine system.
泛素样修饰物 1（UFM1）是一种约二十年前发现的泛素样分子（UBL），但我们对这种新型蛋白质翻译后修饰的细胞和分子机制的了解仍然非常零散。在这篇综述中，我们首先总结了 UFMylation 级联反应中涉及的核心酶和因子，类似于泛素，它是由 UFM1-激活酶 5（UBA5）、UFM1 连接酶 1（UFC1）和 UFM1 特异性连接酶 1（UFL1）依次催化的。受 UFM1 机制在分泌途径中具有重要意义的启发，我们接下来专注于 UFMylation 在维持内质网蛋白稳态中的令人费解的作用，旨在阐明潜在的机制和未来的展望。最后，鉴于强大的内质网网络是健康内分泌分泌细胞的标志，我们强调 UFM1 修饰在胰腺和女性卵巢等内分泌腺的生理学和病理学中的功能，旨在为内分泌系统的其他内部腺体提供精确的见解。
